This proposal explores the neural and psychological mechanisms of cognitive control. Control processes are thought to be an important component of a number of cognitive domains, including attention, working memory, inhibition, episodic memory, categorization, and decision making. Moreover, impairments in cognitive control function are a major component of both psychiatric disorders (e.g., schizophrenia, drug addiction) and healthy aging. A large body of work suggests that the prefrontal cortex (PFC) is a key neural substrate of cognitive control. However, progress in theoretical specification of the mechanisms underlying cognitive control has been slow. The work we propose is a direct extension of our previous efforts to understand and develop explicit models of cognitive control in terms of PFC function and its interaction with other brain structures. We put forth the hypothesis that cognitive control operates in two distinct modes - proactive and reactive - where each is subserved by a separate set of mechanisms. The proactive control mode prepares the cognitive system for upcoming events through the top-down biasing effects of actively sustained PFC representations. The reactive control mode is engaged on as-needed basis, enabling the cognitive system to appropriately respond to imperative events via transient reactivation of PFC, or via retrieval of information stored in posterior cortex and hippocampus. Performance in most cognitive tasks is postulated to rely upon a mixture of proactive and reactive control, but biases towards one mode or another can be influenced by a number of different factors, including: a) specific (and often times subtle) characteristics of the task situation; b) impaired function in the neural systems underlying one mode or another; and c) individual differences in cognitive capabilities and motivation. These hypotheses will be tested in an integrated series of behavioral and neuroimaging studies (using state-of-the-art functional magnetic resonance imaging methods) examining effects of cognitive control mode on brain activation and performance across a wide range of cognitive domains, in both young and older adults, and in relation to individual difference variables. Success in this work would represent a significant theoretical advance, by clarifying the causes and consequences of how control over cognition is achieved. More practically, this project has the potential to provide critical information regarding the neural and psychological bases of both the transient lapses and sustained impairments in cognitive control suffered by both healthy individuals and clinical populations. Such knowledge could be used to drive the development of more effective interventions.